Exercise alters arterial baroreceptor reflex function. However, the central mechanisms that modulate the arterial baroreflex during exercise are not completely understood. Arterial baroreceptor and skeletal muscle receptor afferents are stimulated during exercise and transmit sensory information to the nucleus tractus solitarii (NTS). The NTS is the major sensory nucleus in the mammalian brainstem that processes and relays these inputs to other medullary and supra-medullary nuclei controlling autonomic motor outflow. Previous work during the initial tenure of this award, along with preliminary data for this competitive renewal, has demonstrated that synaptic input from skeletal muscle receptors inhibits arterial baroreceptor signaling by activating local GABAergic and SPergic circuits in the NTS. The specific aims for this application are: 1) to determine the role GABAergic and SPergic mechanisms on central baroreflex control of vagal and sympathetic motor activity; 2) to characterize the synaptic responses of functionally-identified single-unit NTS neurons and to determine the contribution of GABAergic and SPergic receptors on neuronal and network excitability; and 3) to determine the role of innocuous and noxious feedback from skeletal muscle on arterial baroreflex function. To accomplish these aims, physiological paradigms will be used to activate arterial baroreceptors and contraction-sensitive / nociceptive skeletal muscle receptors using an in situ unanesthetized, arterially perfused working heart-brainstem preparation and an in vivo unanesthetized decerebrate preparation in young adult rats. The role of GABAergic and SPergic mechanisms in the NTS will be examined by central microinjections of selective agonists and antagonists for GABA receptors and neurokinin-1 receptors, as well as picoejection of these compounds directly onto functionally identified single-unit NTS neurons using multibarrel microelectrodes. Results from these studies will provide new information regarding the role of NTS neurons in the sensory processing of neural feedback from arterial baroreceptors and skeletal muscle receptors. This knowledge will extend our understanding of the central interaction between baroreceptor and somatic afferents at the level of the NTS and will provide a cellular basis to explain the synaptic mechanisms underlying baroreflex resetting during exercise. [unreadable] [unreadable]